Researchers Look for Answers to Chronic Pain

ANN B. DEBELLIS

Pain affects more Americans than diabetes, heart disease and cancer combined. Because so many people are afflicted by constant pain of some kind, researchers are looking for answers to the many questions in the area of pain management and rehabilitation.

At the University of Alabama at Birmingham, researchers in the Department of Anesthesiology are studying brain images for information about how the body processes pain. Pelvic pain in women is another area being studied.

Ursula Wesselmann, M.D., a long-time researcher at Johns Hopkins University, came to UAB earlier this year, where she focuses her research on pelvic and urogenital pain through two grants from the National Institutes of Health. Chronic pelvic pain is more common in women, she says. Some women present with specific symptoms that seem to be related to the bladder (interstitial cystitis), the uterus (dysmenorrhea), the vagina (vulvodynia), or the gut (irritable bowel syndrome). Others have diffuse chronic pelvic pain that cannot be labeled with any specific diagnosis.

"Historically it was thought that pelvic pain or urogenital pain was due to disease in the reproductive organs, so a lot of women had hysterectomies due to chronic pelvic pain," Wesselmann says. "But the results were often frustrating. Some patients were cured by those surgical interventions, but many were not. It's to the credit of the gynecologists who turned to the pain specialists and said there is something else going on here."

Wesselmann is examining several pathophysiological mechanisms that might be related to women's pelvic pain: immunologic parameters, genetic and neurological aspects, and the influence of early life experience on the development of chronic pelvic pain. "We've looked at models of pain to see if repeated exposure to pain and inflammation results in chronic pain, and we're trying to understand why some people develop chronic pelvic pain and others don't. We're exploring it, but there's no black and white answer," she says. "It is likely that the combination of several mechanisms plays a role in the development of chronic pelvic pain in women."

Wesselmann says looking beyond a specific pelvic organ such as the uterus or bladder has opened a new view into the physiology of pain. If the pain is not coming from the organ, then it must be coming from the central nervous system, so the focus is now on neurological mechanisms. Studies in women with chronic pelvic pain and experimental models are helping Wesselmann identify the nervous system pathways for these pains. Once the pathways are known, the search can be narrowed to neurotransmitters that may be involved. That will provide potential targets for drug design, because there are few drugs designed and FDA-approved specifically for pelvic pain.

For clinical studies, Wesselmann, who will open a clinic at UAB next year for treating pelvic pain, is trying to identify subgroups of patients because research has shown that many patients with visceral pain have other pain syndromes as well. "The same patient might have vaginal pain and interstitial cystitis. They might have irritable bowel syndrome, fibromyalgia or migraine headaches. What we are trying to do in human studies is to identify subgroups of patients who have one type of pelvic pain and those how have many types," she says. "For future clinical trials it will be important to identify those subgroups."

Tim Ness, M.D., Director of Pain Treatment Research at UAB, also works on pelvic pain and is trying to better understand these subgroups. Ness has received funding for a multicenter study to conduct brain imaging in patients with the painful bladder disorder, interstitial cystitis. He and his collaborators want to see what parts of the brain are activated when these patients have a full bladder.

"People in these subgroups appear to be hypersensitive to all pain. Their pain is manifested throughout their bodies," Ness says. "Then there are some who seem to be bladder specific: that's the only part of their body that is hypersensitive."

Ness says that people with hypersensitivity to pain seem to have increased blood flow and activation on both sides of the brain, whereas stimuli to one side of the body usually only shows up in the opposite hemisphere of the brain, not both. He suggests that this may indicate why some people have this global sensitivity. "Treatment may be different for someone with bladder specific pain as opposed to a hypersensitive individual with pain all over," Ness says.

Research in these areas and others related to pain will continue as physicians seek answers to the mysteries of chronic pain and how it affects every patient differently.